15-42068893-G-A

Position:

• chr15-42068893-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178034.4(PLA2G4D):​c.2279C>T​(p.Thr760Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.130

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

PLA2G4D (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17646685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4D	NM_178034.4	c.2279C>T	p.Thr760Ile	missense_variant	20/20	ENST00000290472.4	NP_828848.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4	c.2279C>T	p.Thr760Ile	missense_variant	20/20	1	NM_178034.4	ENSP00000290472.3
PLA2G4D	ENST00000560932.1	n.1432C>T		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.2279C>T (p.T760I) alteration is located in exon 20 (coding exon 20) of the PLA2G4D gene. This alteration results from a C to T substitution at nucleotide position 2279, causing the threonine (T) at amino acid position 760 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Benign	0.059	T
Sift4G	Benign	0.13	T
Polyphen		0.93	P
Vest4		0.12
MutPred		0.44		Loss of disorder (P = 0.0593);
MVP		0.37
MPC		0.12
ClinPred		0.54	D
GERP RS		-3.9
Varity_R		0.11
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42361091;